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Background/Objectives: Abnormalities in cerebrospinal fluid (CSF) dynamics cause diverse conditions, such as hydrocephalus, but the underlying mechanism is still unknown. Methods to study CSF dynamics in small animals have not been established due to the lack of an evaluation system. Therefore, the purpose of this research study is to establish the time-spatial labeling inversion pulse (Time-SLIP) MRI technique for the evaluation of CSF dynamics in mice. Methods: We performed the Time-SLIP technique on 10 wild-type mice and 20 Tiptoe-walking Yoshimura (TWY) mice, a mouse model of ossification of the posterior longitudinal ligament (OPLL). We defined the stir distance as the distance of CSF stirring and calculated the mean ± standard deviation. The intraclass correlation coefficient of intraobserver reliability was also calculated. Furthermore, in TWY mice, the correlation coefficient between stir distance and canal stenosis ratio (CSR) was calculated. Results: The stir distance was significantly lower in TWY mice at 12 weeks and 17 weeks of age (1.20 ± 0.16, 1.21 ± 0.06, and 1.21 ± 0.15 mm at 12 weeks and 1.32 ± 0.21, 1.28 ± 0.23, and 1.38 ± 0.31 mm at 17 weeks for examiners A, B, and C). The intrarater reliability of the three examiners was excellent (>0.90) and there was a strongly negative correlation between stir distance and CSR in TWY mice (>-0.80). Conclusions: In this study, we established the Time-SLIP technique in experimental mice. This technique allows for a better understanding of CSF dynamics in small laboratory animals.
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Adolescent idiopathic scoliosis (AIS) affects approximately 3% of the global population. Recent studies have drawn attention to abnormalities in the dynamics of the CSF as potential contributors. This research aims to employ the Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRI to assess and analyze cerebrospinal fluid (CSF) dynamics in AIS patients. 101 AIS patients underwent Time-SLIP MRI. Images were taken at the mid-cervical and craniocervical junction regions. The sum of the maximum movement distances of CSF on the ventral and dorsal sides of the spinal canal within a single timeframe was defined and measured as Travel Distance (TD). Correlations between TD, age, Cobb angle, and Risser grade were analyzed. TD comparisons were made across Lenke classifications. TD for all patients was a weak correlation with the Cobb angle (r = - 0.16). Comparing TD between Lenke type 1 and 5, type 5 patients display significantly shorter TD (p < 0.05). In Risser5 patients with Lenke type 5 showed a significant negative correlation between Cobb angle and TD (r = - 0.44). Lenke type 5 patients had significantly shorter CSF TD compared to type1, correlating with worsening Cobb angles. Further analysis and exploration are required to understand the mechanism of onset and progression.
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Líquido Cefalorraquídeo , Imagen por Resonancia Magnética , Escoliosis , Humanos , Escoliosis/diagnóstico por imagen , Adolescente , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , NiñoRESUMEN
Animal models of brain function are critical for the study of human diseases and development of effective interventions. Resting-state network (RSN) analysis is a powerful tool for evaluating brain function and performing comparisons across animal species. Several studies have reported RSNs in the common marmoset (Callithrix jacchus; marmoset), a non-human primate. However, it is necessary to identify RSNs and evaluate commonality and inter-individual variance through analyses using a larger amount of data. In this study, we present marmoset RSNs detected using > 100,000 time-course image volumes of resting-state functional magnetic resonance imaging data with careful preprocessing. In addition, we extracted brain regions involved in the composition of these RSNs to understand the differences between humans and marmosets. We detected 16 RSNs in major marmosets, three of which were novel networks that have not been previously reported in marmosets. Since these RSNs possess the potential for use in the functional evaluation of neurodegenerative diseases, the data in this study will significantly contribute to the understanding of the functional effects of neurodegenerative diseases.
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Callithrix , Enfermedades Neurodegenerativas , Animales , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Mapeo Encefálico/métodosRESUMEN
ABSTRACT: Magnetic resonance imaging (MRI) is a crucial imaging technique for visualizing water in living organisms. Besides proton MRI, which is widely available and enables direct visualization of intrinsic water distribution and dynamics in various environments, MR-WTI (MR water tracer imaging) using 17 O-labeled water has been developed, benefiting from the many advancements in MRI software and hardware that have substantially improved the signal-to-noise ratio and made possible faster imaging. This cutting-edge technique allows the generation of novel and valuable images for clinical use. This review elucidates the studies related to MRI water tracer techniques centered around 17 O-labeled water, explaining the fundamental principles of imaging and providing clinical application examples. Anticipating continued progress in studies involving isotope-labeled water, this review is expected to contribute to elucidating the pathophysiology of various diseases related to water dynamics abnormalities and establishing novel imaging diagnostic methods for associated diseases.
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Imagen por Resonancia Magnética , Programas Informáticos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodosRESUMEN
Background: Spinal cord injury (SCI) causes severe sequelae and significant social loss, depending on the extent of the damage. Most previous studies have focused on the pathology of the spinal cord to develop treatments for SCI. However, it is now known that the brain, which is not directly damaged, also undergoes morphological changes after spinal cord injury, which could affect natural recovery and treatment. In recent years, magnetic resonance imaging (MRI) has been developed to analyze functional changes in the brain. Resting-state functional MRI (rsfMRI), which captures brain activity at rest, can calculate functional connections between brain areas and identify central hubs by network analysis. Purpose: We aim to investigate functional connectivity in the brain using rsfMRI after SCI and to determine how brain-network main hubs change over time. Methods: We evaluated rsfMRI in 10 mice of the contusional SCI model and calculated connectivity using graph theory. We evaluated "centrality," a representative parameter of network analysis. The subtype of centrality was degree centrality, which indicates the hub function of a single area. The five times of rsfMRI were performed in each individual mouse: before injury and at 1, 3, 7, and 14 weeks post-injury. Results: Before the injury, the degree centralities of the primary and secondary motor cortex were high, suggesting that these motor cortices served as main hubs for motor function. After SCI, the hub function of the motor cortices decreased by 14 weeks. In contrast, hub function in the external capsule and the putamen comparatively increased with time after injury, suggesting that the extrapyramidal/subcortical system, which runs the ventral side of the spinal cord and remains after injury in this model, becomes dominant. Conclusion: We demonstrated the shift of the brain network hub after SCI. The results of this study provide basic information for understanding brain network changes after SCI and would be useful for treatment selection and evaluation of its efficacy in SCI patients.
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The development of regenerative medicine using cell therapy is eagerly awaited for diseases such as spinal cord injury (SCI), for which there has been no radical cure. We previously reported the direct conversion of human fibroblasts into neuronal-like cells using only chemical compounds; however, it is unclear whether chemical compound-induced neuronal-like (CiN) cells are clinically functional. In this study, we partially modified the method of inducing CiN cells (termed immature CiN cells) and examined their therapeutic efficacy, in a rat model of SCI, to investigate whether immature CiN cells are promising for clinical applications. Motor function recovery, after SCI, was assessed using the Basso, Beattie, and Bresnahan (BBB) test, as well as the CatWalk analysis. We found that locomotor recovery, after SCI in the immature CiN cell-transplanted group, was partially improved compared to that in the control group. Consistent with these results, magnetic resonance imaging (MRI) and histopathological analyses revealed that nerve recovery or preservation improved in the immature CiN cell-transplanted group. Furthermore, transcriptome analysis revealed that immature CiN cells highly express hepatocyte growth factor (HGF), which has recently been shown to be a promising therapeutic agent against SCI. Our findings suggest that immature CiN cells may provide an alternative strategy for the regenerative therapy of SCI.
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Fibroblastos , Traumatismos de la Médula Espinal , Humanos , Animales , Ratas , Tratamiento Basado en Trasplante de Células y Tejidos , Perfilación de la Expresión Génica , Recuperación de la Función , Traumatismos de la Médula Espinal/terapiaRESUMEN
Common marmosets are promising laboratory animals for the study of higher brain functions. Although there are many opportunities to use sedatives and anesthetics in resting brain function measurements in marmosets, their effects on the resting-state network remain unclear. In this study, the effects of sedatives or anesthetics such as midazolam, dexmedetomidine, co-administration of isoflurane and dexmedetomidine, propofol, alfaxalone, isoflurane, and sevoflurane on the resting brain function in common marmosets were evaluated using independent component analysis, dual regression analysis, and graph-theoretic analysis; and the sedatives or anesthetics suitable for the evaluation of resting brain function were investigated. The results show that network preservation tendency under light sedative with midazolam and dexmedetomidine is similar regardless of the type of target receptor. Moreover, alfaxalone, isoflurane, and sevoflurane have similar effects on resting state brain function, but only propofol exhibits different tendencies, as resting brain function is more preserved than it is following the administration of the other anesthetics. Co-administration of isoflurane and dexmedetomidine shows middle effect between sedatives and anesthetics.
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Anestésicos , Dexmedetomidina , Isoflurano , Propofol , Animales , Hipnóticos y Sedantes/farmacología , Callithrix , Isoflurano/farmacología , Sevoflurano/farmacología , Midazolam/farmacología , Dexmedetomidina/farmacología , Anestésicos/farmacología , EncéfaloRESUMEN
Caffeine is a psychoactive substance that not only improves wakefulness, but also slows the cognitive decline caused by aging. However, at present, there are no reports about the effects of caffeine withdrawal, including headaches and changes in brain functional networks (nerve activity). Headache may occur approximately 24 h after discontinuing caffeine intake in chronic caffeine drinkers. The current study aimed to examine the brain functional activity via resting-state functional magnetic resonance imaging in chronically caffeinated and decaffeinated groups to investigate changes in brain activity caused by caffeine. C57BL/6J mice were included in the analysis, and they underwent 9.4-T ultrahigh-field magnetic resonance imaging. The mice were classified into the control, chronic caffeinated, and caffeine withdrawal grsoups. Mice were divided into three groups: 1) not exposed to caffeine (control); 2) treated with caffeine at a concentration of 0.3 mg/mL for 4 weeks (chronic caffeinated); and 3) treated as before with caffeine and withdrawn from caffeine for 24 h. After the three groups were examined, functional connectivity matrices were calculated using brain imaging analysis tools, and independent component analysis was performed. The results showed that caffeine administration activated neural activity areas in the stress response system. Furthermore, 24h after caffeine withdrawal, the results showed an increase in pain-related neural activity. In addition, caffeine administration was shown to activate the dentate gyrus, one of the hippocampal regions, and to decrease the neural activity in the olfactory bulb and anterior cingulate cortex. In the current research, the neural activity of specific brain regions changed after chronic caffeine administration and withdrawal.
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Alzheimer's disease (AD) is the leading cause of dementia which afflicts tens of millions of people worldwide. Despite many scientific progresses to dissect the AD's molecular basis from studies on various mouse models, it has been suffered from evolutionary species differences. Here, we report generation of a non-human primate (NHP), common marmoset model ubiquitously expressing Amyloid-beta precursor protein (APP) transgenes with the Swedish (KM670/671NL) and Indiana (V717F) mutations. The transgene integration of generated two transgenic marmosets (TG1&TG2) was thoroughly investigated by genomic PCR, whole-genome sequencing, and fluorescence in situ hybridization. By reprogramming, we confirmed the validity of transgene expression in induced neurons in vitro. Moreover, we discovered structural changes in specific brain regions of transgenic marmosets by magnetic resonance imaging analysis, including in the entorhinal cortex and hippocampus. In immunohistochemistry, we detected increased Aß plaque-like structures in TG1 brain at 7 years old, although evident neuronal loss or glial inflammation was not observed. Thus, this study summarizes our attempt to establish an NHP AD model. Although the transgenesis approach alone seemed not sufficient to fully recapitulate AD in NHPs, it may be beneficial for drug development and further disease modeling by combination with other genetically engineered models and disease-inducing approaches.
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Enfermedad de Alzheimer , Precursor de Proteína beta-Amiloide , Animales , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Encéfalo/metabolismo , Callithrix/genética , Modelos Animales de Enfermedad , Hibridación Fluorescente in Situ , Ratones Transgénicos , TransgenesRESUMEN
Rett syndrome (RTT) is a severe progressive neurodevelopmental disorder characterized by various neurological symptoms. Almost all RTT cases are caused by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) gene, and several mouse models have been established to understand the disease. However, the neuroanatomical abnormalities in each brain region of RTT mouse models have not been fully understood. Here, we investigated the global and local neuroanatomy of the Mecp2 gene-deleted RTT model (Mecp2-KO) mouse brain using T2-weighted 3D magnetic resonance imaging with different morphometry to clarify the brain structural abnormalities that are involved in the pathophysiology of RTT. We found a significant reduction in global and almost all local volumes in the brain of Mecp2-KO mice. In addition, a detailed comparative analysis identified specific volume reductions in several brain regions in the Mecp2-deficient brain. Our analysis also revealed that the Mecp2-deficient brain shows changes in hemispheric asymmetry in several brain regions. These findings suggest that MeCP2 affects not only the whole-brain volume but also the region-specific brain structure. Our study provides a framework for neuroanatomical studies of a mouse model of RTT.
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A brain atlas is necessary for analyzing structure and function in neuroimaging research. Although various annotation volumes (AVs) for the mouse brain have been proposed, it is common in magnetic resonance imaging (MRI) of the mouse brain that regions-of-interest (ROIs) for brain structures (nodes) are created arbitrarily according to each researcher's necessity, leading to inconsistent ROIs among studies. One reason for such a situation is the fact that earlier AVs were fixed, i.e. combination and division of nodes were not implemented. This report presents a pipeline for constructing a flexible annotation atlas (FAA) of the mouse brain by leveraging public resources of the Allen Institute for Brain Science on brain structure, gene expression, and axonal projection. A mere two-step procedure with user-specified, text-based information and Python codes constructs FAA with nodes which can be combined or divided objectively while maintaining anatomical hierarchy of brain structures. Four FAAs with total node count of 4, 101, 866, and 1381 were demonstrated. Unique characteristics of FAA realized analysis of resting-state functional connectivity (FC) across the anatomical hierarchy and among cortical layers, which were thin but large brain structures. FAA can improve the consistency of whole brain ROI definition among laboratories by fulfilling various requests from researchers with its flexibility and reproducibility.
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Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Imagen por Resonancia Magnética/métodos , Red Nerviosa/anatomía & histología , Proteínas del Tejido Nervioso/genética , Neuroimagen/métodos , Animales , Atlas como Asunto , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Mapeo Encefálico/normas , Expresión Génica , Perfilación de la Expresión Génica , Imagen por Resonancia Magnética/normas , Masculino , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/metabolismo , Proteínas del Tejido Nervioso/clasificación , Proteínas del Tejido Nervioso/metabolismo , Neuroimagen/normas , Vigilia/fisiologíaRESUMEN
The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation was investigated using TGN-020, an aquaporin 4 (AQP4) channel blocker, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, but not in the DfMRI responses which remained unsensitive to astrocyte function perturbation.
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Acuaporina 4/antagonistas & inhibidores , Astrocitos/metabolismo , Mapeo Encefálico/métodos , Corteza Visual/fisiología , Animales , Astrocitos/citología , Imagen de Difusión por Resonancia Magnética/métodos , Masculino , Ratones , Ratones Endogámicos C57BL , Niacinamida/análogos & derivados , Niacinamida/farmacología , Tiadiazoles/farmacologíaRESUMEN
The degree of intervertebral disc (IVD) degeneration is qualitatively evaluated on T2-weighted imaging (T2WI). However, it is difficult to assess subtle changes in IVD degeneration using T2WI. Q-space imaging (QSI) is a quantitative diffusion-weighted imaging modality used to detect subtle changes in microenvironments. This study aimed to evaluate whether QSI can detect the inhibitory effects of the antioxidant N-acetylcysteine (NAC) in IVD degeneration. We classified female Wistar rats into control, puncture, and NAC groups (n = 5 per group). In the puncture and NAC groups, IVDs were punctured using a needle. The antioxidant NAC, which suppresses the progression of IVD degeneration, was orally administered in the NAC group 1 week prior to puncture. The progression and inhibitory effect of NAC in IVD degeneration were assessed using magnetic resonance imaging (MRI): IVD height, T2 mapping, apparent diffusion coefficient (ADC), and QSI. MRI was performed using a 7-Tesla system with a conventional probe (20 IVDs in each group). QSI parameters that were assessed included Kurtosis, the probability at zero displacement (ZDP), and full width at half maximum (FWHM). IVD degeneration by puncture was confirmed by histology, IVD height, T2 mapping, ADC, and all QSI parameters (P < .001); however, the inhibitory effect of NAC was confirmed only by QSI parameters (Kurtosis and ZDP: both P < .001; FWHM: P < .01). Kurtosis had the largest effect size (Kurtosis: 1.13, ZDP: 1.06, and FWHM: 1.02) when puncture and NAC groups were compared. QSI has a higher sensitivity than conventional quantitative methods for detecting the progressive change and inhibitory effect of NAC in IVD degeneration.
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Acetilcisteína/uso terapéutico , Imagen de Difusión por Resonancia Magnética/métodos , Depuradores de Radicales Libres/uso terapéutico , Degeneración del Disco Intervertebral/diagnóstico por imagen , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Degeneración del Disco Intervertebral/tratamiento farmacológico , Ratas WistarRESUMEN
STUDY DESIGN: Cross-sectional study. OBJECTIVE: Patients who undergo intramedullary spinal surgery occasionally experience post-surgical chronic pain; however, the underlying mechanisms are not yet completely understood. Therefore, this study aimed to identify the cerebral structural changes in patients with post-surgical chronic myelopathic pain using voxel-based morphometry. SETTING: Single university hospital in Tokyo, Japan. METHODS: Forty-nine patients who had undergone intramedullary spinal surgery between January 2002 and April 2014 participated in this study. Participants were classified into two groups based on their post-surgical chronic pain intensity: control (numeric rating scale score of <3) and pain (numeric rating scale score of ≥3) groups. We compared pain questionnaire and brain MRI between two groups. Brain MRI data of each participants was analyzed using voxel-based morphometry. RESULTS: Voxel-based morphometry revealed that the gray matter volume in the left supplementary motor area, left primary motor area, and left posterior cingulate cortex was higher in the pain group than that in the control group. In addition, the numeric rating scale score was significantly correlated with increased gray matter volume in the left primary motor area, left posterior cingulate cortex, and right superior parietal lobule. CONCLUSION: Present study elucidates the characteristic cerebral structural changes after an intramedullary spinal surgery using voxel-based morphometry and indicates that the structural changes in specific cerebral areas are associated with post-surgical chronic myelopathic pain.
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Dolor Crónico/fisiopatología , Sustancia Gris/patología , Giro del Cíngulo/patología , Corteza Motora/patología , Neuroimagen , Procedimientos Neuroquirúrgicos/efectos adversos , Dolor Postoperatorio/fisiopatología , Enfermedades de la Médula Espinal/cirugía , Adulto , Anciano , Dolor Crónico/etiología , Femenino , Sustancia Gris/diagnóstico por imagen , Giro del Cíngulo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Corteza Motora/diagnóstico por imagen , Neuroimagen/métodos , Dolor Postoperatorio/etiologíaRESUMEN
Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.
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Encéfalo/fisiología , Conectoma/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Red Nerviosa/fisiología , Animales , Encéfalo/diagnóstico por imagen , Conectoma/normas , Femenino , Procesamiento de Imagen Asistido por Computador/normas , Imagen por Resonancia Magnética/normas , Masculino , Ratones , Ratones Endogámicos C57BL , Red Nerviosa/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
Baseline locomotion and behavioral traits in the common marmoset Parkinson's disease model were examined to provide basic information for preclinical evaluations of medical treatments. A single regimen of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine at a cumulative dose of 5 mg/kg as the free base over three consecutive days was administered subcutaneously to 10 marmosets. Data obtained from these marmosets were compared to pre-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine levels or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine free marmosets. After the single regimen, reduced daily locomotion, a measure of immobility (a primary sign of Parkinsonism), was observed for more than a year. A moving tremor was also observed by visual inspection during this period. When apomorphine (0.13 mg/kg, s.c.) was administered, either right or left circling behavior was observed in a cylindrical chamber in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets, suggestive of unequal neural damage between the two brain hemispheres to different extents. MRI revealed that T1 relaxation time in the right substantia nigra correlated with right circling in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine marmosets. Histology was supportive of dopaminergic neural loss in the striatum. These results increase our understanding of the utility and limitations of the Parkinson's disease model in marmosets with a single 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine regimen, and provide reference data for efficacious preclinical evaluations.
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Locomoción/fisiología , Enfermedad de Parkinson/patología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/patología , Callithrix/fisiología , Cuerpo Estriado/patología , Modelos Animales de Enfermedad , Dopamina/metabolismo , Locomoción/efectos de los fármacos , Trastornos Parkinsonianos/patología , Sustancia Negra/patología , Temblor/inducido químicamenteRESUMEN
The common marmoset (Callithrix jacchus) is a non-human primate that provides valuable models for neuroscience and aging research due to its anatomical similarities to humans and relatively short lifespan. This study was carried out to examine whether aged marmosets develop glaucoma, as seen in humans. We found that 11% of the aged marmosets presented with glaucoma-like characteristics; this incident rate is very similar to that in humans. Magnetic resonance imaging showed a significant volume loss in the visual cortex, and histological analyses confirmed the degeneration of the lateral geniculate nuclei and visual cortex in the affected marmosets. These marmosets did not have elevated intraocular pressure, but showed an increased oxidative stress level, low cerebrospinal fluid (CSF) pressure, and low brain-derived neurotrophic factor (BDNF) and TrkB expression in the retina, optic nerve head and CSF. Our findings suggest that marmosets have potential to provide useful information for the research of eye and the visual system.
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Factor Neurotrófico Derivado del Encéfalo/metabolismo , Glaucoma de Baja Tensión , Disco Óptico/metabolismo , Receptor trkB/metabolismo , Corteza Visual , Envejecimiento , Animales , Callithrix , Modelos Animales de Enfermedad , Femenino , Glaucoma de Baja Tensión/metabolismo , Glaucoma de Baja Tensión/fisiopatología , Masculino , Retina/metabolismo , Corteza Visual/metabolismo , Corteza Visual/fisiopatologíaRESUMEN
BACKGROUND: Skeletal muscles include fast and slow muscle fibers. The tibialis anterior muscle (TA) is mainly composed of fast muscle fibers, whereas the soleus muscle (SOL) is mainly composed of slow muscle fibers. However, a noninvasive approach for appropriately investigating the characteristics of muscles is not available. Monitoring of skeletal muscle characteristics can help in the evaluation of the effects of strength training and diseases on skeletal muscles. PURPOSE: The present study aimed to determine whether q-space imaging can distinguish between TA and SOL in in vivo mice. METHODS: In vivo magnetic resonance imaging of the right calves of mice (n = 8) was performed using a 7-Tesla magnetic resonance imaging system with a cryogenic probe. TA and SOL were assessed. q-space imaging was performed with a field of view of 10 mm × 10 mm, matrix of 48 × 48, and section thickness of 1000 µm. There were ten b-values ranging from 0 to 4244 s/mm2, and each b-value had diffusion encoding in three directions. Magnetic resonance imaging findings were compared with immunohistological findings. RESULTS: Full width at half maximum and Kurtosis maps of q-space imaging showed signal intensities consistent with immunohistological findings for both fast (myosin heavy chain II) and slow (myosin heavy chain I) muscle fibers. With regard to quantification, both full width at half maximum and Kurtosis could represent the immunohistological findings that the cell diameter of TA was larger than that of SOL (P < 0.01). CONCLUSION: q-space imaging could clearly differentiate TA from SOL using differences in cell diameters. This technique is a promising method to noninvasively estimate the fiber type ratio in skeletal muscles, and it can be further developed as an indicator of muscle characteristics.
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Imagen de Difusión por Resonancia Magnética/métodos , Fibras Musculares de Contracción Rápida/fisiología , Fibras Musculares de Contracción Lenta/fisiología , Músculo Esquelético/diagnóstico por imagen , Animales , Tamaño de la Célula , Imagen de Difusión por Resonancia Magnética/estadística & datos numéricos , Femenino , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Contracción Muscular/fisiología , Fibras Musculares de Contracción Rápida/citología , Fibras Musculares de Contracción Lenta/citología , Músculo Esquelético/citología , Músculo Esquelético/fisiología , Cadenas Pesadas de Miosina/metabolismoRESUMEN
Intervertebral disk (IVD) degeneration is often associated with severity of lower back pain. IVD core is an avascular, highly hydrated tissue composed of type II collagen, glycosaminoglycans, and proteoglycans. The disk degeneration is not only a destruction of IVD structure but also is related to a disorder of the turnover of the disk matrix, leading the jelly-like IVD core to be replaced by fibrous components. Here we present a disease-modifying strategy for IVD degenerative diseases by direct regulation of the cells in the IVD using mRNA medicine, to alter the misbalanced homeostasis during disk degeneration. When mRNA encoding a cartilage-anabolic transcription factor, runt-related transcription factor-1, was administered to a rat model of coccygeal disk degeneration using a polyplex nanomicelle composed of polyethylene glycol-polyamino acid block copolymers and mRNA, the disk height was maintained to a significantly higher extent (≈81%) compared to saline control (69%), with prevention of fibrosis in the disk tissue. In addition, the use of nanomicelles effectively prevented inflammation, which was observed by injection of naked mRNA into the disk. This proof-of-concept study revealed that mRNA medicine has a potential for treating IVD degenerative diseases by introducing a cartilage-anabolic factor into the host cells, proposing a new therapeutic strategy using mRNA medicine.
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Striatal medium spiny neurons (MSNs) control motor function. Hyper- or hypo-activity of MSNs coincides with basal ganglia-related movement disorders. Based on the assumption that lasting alterations in neuronal activity lead to structural changes in the brain, understanding these structural alterations may be used to infer MSN functional abnormalities. To infer MSN function from structural data, understanding how long-lasting alterations in MSN activity affect brain morphology is essential. To address this, we utilized a simplified model of functional induction by stimulating MSNs expressing channelrhodopsin 2 (ChR2). Subsequent structural alterations which induced long-term activity changes in these MSNs were investigated in the striatal pathway and its associated regions by diffusion tensor imaging (DTI) and histological assessment with super-resolution microscopy. DTI detected changes in the striatum, substantia nigra, and motor cortex. Histological assessment found a reduction in the diameter of myelinated cortical axons as well as MSN dendrites and axons. The structural changes showed a high correlation between DTI parameters and histological data. These results demonstrated that long-term neural activation in the MSNs alters the diameter of MSN and cortical neurons fibers. This study provides a tool for understanding the causal relationship between functional and structural alterations.